Impact of Prophylactic Cranial Irradiation on Neurocognitive Function in Patients With Small Cell Lung Carcinoma

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: November 9, 2006

Presenter: D.R. Grosshans
Presenter's Affiliation: MD Andersen Cancer Center, Houston, TX
Type of Session: Scientific


  • Numerous reports have shown that limited-stage small cell lung cancer patients who receive prophylactic cranial irradiation (PCI), after achieving a clinical complete response from definitive thoracic treatment, have increased survival.
  • However, some physicians withhold PCI because of fear of severe neurological decline after cranial radiation.
  • The most commonly cited study about neurocognitive decline following brain radiation is from 1989 (DeAngelis et al).
  • That study is a retrospective review of cranial radiation for known brain metastases (i.e. not prophylactic) and included several unconventional fractionation schemes (including 500 and 600 cGy fractions).
  • Previous studies about neurocognitive decline after PCI are retrospective, have limited follow-up, and may have lacked baseline assessments or employed suboptimal testing methods.
  • Mini mental status examinations are only designed to detect severe dementia or delirium.
  • Modern neurocognitive testing measures capabilities necessary for daily life.

Materials and Methods

  • This study had baseline neurocognitive testing performed in all patients before radiation.
  • The neurocognitive testing in this study measured attention, learning and memory, processing speed, executive function, abstract reasoning, language, and motor coordination.
  • The study was performed between 1989 and 2002.
  • 96 patients were prospectively followed for a median time of 23 months (range from 6 to 120 months).
  • 93 patients had limited stage small cell lung cancer, and 3 had extensive stage small cell lung cancer.
  • All patients had to have a complete response to therapy before receiving PCI.
  • All patients received 25Gy in 10 fractions.
  • Of the original 96 patients, 69 received PCI.


  • A large number of patients were found to have baseline neurocognitive deficits even before PCI (38% with executive function, 43% with learning and memory, 30% with processing speed, and 30% with motor coordination).
  • Of the 69 patients who received PCI, 37 had repeat neurocognitive testing.
  • On multivariate analysis, the use of PCI was not statistically correlated to any change from baseline in measures of attention, learning and memory, processing speed, executive function, abstract reasoning, language and motor coordination, no matter what time point was analyzed.

Author's Conclusions

  • This study was prospective, used meticulous neurocognitive testing, had baseline assessments, and long-term follow-up.
  • Now that this study has dmonstrated that PCI does not carry with it any significant risk of  cognitive decline, it should be considered the standard of care for patients who have had a complete clinical response to treatment of their small cell lung cancer.
  • A large percentage of patients have baseline neurocognitive deficits before PCI.

Clinical/Scientific Implications

The authors of this study reported the results of an interesting, large, and well-designed study of PCI with important conclusions.  The authors used a conventional radiation scheme of low dose per fraction compared with previous reports, and they saw no correlation between PCI and neurocognitive deficits.  The authors’ conclusions are valid, and PCI should be considered the standard of care for patients with a complete response to therapy for small cell lung cancer.  One of the most interesting questions raised by this study is why so many of the patients had baseline neurocognitive deficits before PCI?  Could this represent a chemotherapy effect?  It would be interesting to perform a similar study whereby the baseline testing was performed before any systemic therapy was given.